晚期非小细胞肺癌（NSCLC）患者的治疗方式在过去的10年中发生了巨大的变化，这主要得益于多种靶向肿瘤驱动基因的酪氨酸激酶抑制剂（TKI）的出现和发展。其中，携带导致3-5％所有晚期NSCLC的间变性淋巴瘤激酶（ALK）易位的患者，其临床结果得到了显著的改善，将5年的生命预期从不到5％增加到50％。事实上，多种ALK抑制剂（ALKi）已进入ALK +患者的治疗算法，扩大了他们的治疗选择机会。值得注意的是，在不久的将来，我们可以利用多达6种不同分子的一线治疗方法（克唑替尼，赛松尼，阿来替尼，布里加替尼，加上恩沙替尼和洛拉替尼）。在可用的ALKi中，第二代（2G）抑制剂布里加替尼在这种情况下表现出显著的活性，同时还可以治疗中枢神经系统（CNS）疾病，并具有良好的安全性，支持其作为一线治疗在 ALTA-1L试验结果的基础上批准。布里加替尼具有独特的酶靶点配置，是ALK靶向旅程中的有价值的机会，尽管需要平衡其安全性。这些患者的治疗选择丰富，提出了重要的问题。在没有直接效果比较的情况下，很难定义最佳方法，并且更难确定正确的管理顺序，以便为ALK +肺癌患者提供最佳治疗机会。在如此多样化的选择中，我们回顾了布里加替尼的临床前和临床疗效数据，以及其药理和安全性，以及在ALK + NSCLC情况下的实际和潜在的未来应用。通过创建与其他可用2G ALKi的间接比较的虚假练习，我们希望总结出选择正确时间的最佳药物所需的知识。此外，我们还回顾了可用的分子耐药机制数据和推测的治疗应用程序，例如ROS1 + NSCLC患者或进展至奥西替尼的EGFR +患者。

The treatment landscape of advanced non-small cell lung cancer (NSCLC) patients has dramatically changed over the past 10 years, particularly thanks to the advent and development of several tyrosine kinase inhibitors (TKI) targeting oncogenic drivers. Among them, patients bearing anaplastic lymphoma kinase (ALK) translocations, which are causative of 3-5% of all advanced NSCLC, have seen dramatically improved their clinical outcomes moving life expectancy at 5 years from less than 5% to 50%. In fact, multiple ALK inhibitors (ALKi) entered in the therapeutic algorithm of ALK+ patients, multiplying their treatment opportunities. Remarkably, in the near future we could take advantage of up to different 6 molecules for the first-line approach (crizotinib, ceritinib, alectinib, brigatinib, plus ensartinib and lorlatinib). Among available ALKi, brigatinib, a second-generation (2G) inhibitor, showed notable activity in this setting, also against central nervous system (CNS) disease, and a good safety profile, supporting its approval as upfront treatment based on the ALTA-1L trial results. With a peculiar profile of enzymatic targets, brigatinib represents a valuable opportunity in the ALK targeting journey, albeit having to balance its safety profile. The abundance of therapeutic options for these patients poses nontrivial questions; in absence of direct comparisons of efficacy is not easy to define the best approach and, more compelling, the correct administration sequence in order to give the best therapeutic chances to ALK+ lung cancer patients. In such wide variety of options, we reviewed the preclinical and clinical efficacy data of brigatinib, its pharmacological and safety profile, like also actual and potential future applications in the ALK+ NSCLC scenario. Through a spurious exercise of an indirect comparison with other available 2G ALKi, we tent to summarize the required knowledge to properly choose the best drug at the right time. Furthermore, we reviewed available data on molecular resistance mechanisms and putative therapeutic applications in other contexts, such as ROS1+ NSCLC patients or EGFR+ ones progressing to osimertinib.